Cysteine residues are essential for dimerization of Hippo pathway components YAP2L and TAZ

Abstract Hippo signalling pathway is an emerging signalling pathway that plays important roles in organ size control, tumorigenesis, metastasis, stress response, apoptosis, stem cell differentiation and renewal during development and tissue homeostasis. Recent studies reported that human serine/thre...

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Autores principales: Prem Khanal, Zongchao Jia, Xiaolong Yang
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Publicado: Nature Portfolio 2018
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spelling oai:doaj.org-article:937f5fb63a0a43d4a7328c608d9245072021-12-02T11:40:24ZCysteine residues are essential for dimerization of Hippo pathway components YAP2L and TAZ10.1038/s41598-018-21828-62045-2322https://doaj.org/article/937f5fb63a0a43d4a7328c608d9245072018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-21828-6https://doaj.org/toc/2045-2322Abstract Hippo signalling pathway is an emerging signalling pathway that plays important roles in organ size control, tumorigenesis, metastasis, stress response, apoptosis, stem cell differentiation and renewal during development and tissue homeostasis. Recent studies reported that human serine/threonine protein kinase, Mst1, a core component of the Hippo pathway can be activated through formation of homodimer. However, it is still unclear whether or not other components of the Hippo pathway are also regulated through dimerization. Here we provide the first evidence that Hippo components and oncoprotein YAP2L and TAZ can form homodimer in vitro and in vivo by forming disulphide bond through cysteine residue(s). We have also shown that the homodimers of YAP2L/TAZ are more stable and showed more oncogenic behaviour than their corresponding monomers as revealed by colony formation and cell transformation assay. Since cysteine post-translational regulation plays important roles in redox signalling, tumorigenesis and drug resistance, further studies on the functional effect of this dimerization through post-translational modulation of cysteine residues in YAP2L/TAZ will provide a significant contribution to our understanding of the roles of YAP2L/TAZ in cancer development and therapy.Prem KhanalZongchao JiaXiaolong YangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Prem Khanal
Zongchao Jia
Xiaolong Yang
Cysteine residues are essential for dimerization of Hippo pathway components YAP2L and TAZ
description Abstract Hippo signalling pathway is an emerging signalling pathway that plays important roles in organ size control, tumorigenesis, metastasis, stress response, apoptosis, stem cell differentiation and renewal during development and tissue homeostasis. Recent studies reported that human serine/threonine protein kinase, Mst1, a core component of the Hippo pathway can be activated through formation of homodimer. However, it is still unclear whether or not other components of the Hippo pathway are also regulated through dimerization. Here we provide the first evidence that Hippo components and oncoprotein YAP2L and TAZ can form homodimer in vitro and in vivo by forming disulphide bond through cysteine residue(s). We have also shown that the homodimers of YAP2L/TAZ are more stable and showed more oncogenic behaviour than their corresponding monomers as revealed by colony formation and cell transformation assay. Since cysteine post-translational regulation plays important roles in redox signalling, tumorigenesis and drug resistance, further studies on the functional effect of this dimerization through post-translational modulation of cysteine residues in YAP2L/TAZ will provide a significant contribution to our understanding of the roles of YAP2L/TAZ in cancer development and therapy.
format article
author Prem Khanal
Zongchao Jia
Xiaolong Yang
author_facet Prem Khanal
Zongchao Jia
Xiaolong Yang
author_sort Prem Khanal
title Cysteine residues are essential for dimerization of Hippo pathway components YAP2L and TAZ
title_short Cysteine residues are essential for dimerization of Hippo pathway components YAP2L and TAZ
title_full Cysteine residues are essential for dimerization of Hippo pathway components YAP2L and TAZ
title_fullStr Cysteine residues are essential for dimerization of Hippo pathway components YAP2L and TAZ
title_full_unstemmed Cysteine residues are essential for dimerization of Hippo pathway components YAP2L and TAZ
title_sort cysteine residues are essential for dimerization of hippo pathway components yap2l and taz
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/937f5fb63a0a43d4a7328c608d924507
work_keys_str_mv AT premkhanal cysteineresiduesareessentialfordimerizationofhippopathwaycomponentsyap2landtaz
AT zongchaojia cysteineresiduesareessentialfordimerizationofhippopathwaycomponentsyap2landtaz
AT xiaolongyang cysteineresiduesareessentialfordimerizationofhippopathwaycomponentsyap2landtaz
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